调节性 T 细胞 (Treg) 在肿瘤微环境中发挥着重要作用。然而，人们对其免疫抑制作用背后的机制知之甚少。我们发现肿瘤浸润性 Tregs 中的 CCR6-CCL20 活性与更大的糖酵解活性相关，Ccr6 的消除减少了糖酵解和乳酸的产生，同时增加了代偿性谷氨酰胺代谢。由于激活诱导的糖酵解减少，Ccr6-/- Tregs 中对 CD8 T 细胞的免疫抑制活性被消除。此外，与野生型小鼠相比，Ccr6-/- 小鼠在多种肿瘤模型中表现出更好的存活率，并且 Treg 和 CD8 T 细胞耗竭消除了这种改善。此外，Ccr6消融进一步提高了临床前神经胶质瘤模型中抗PD-1治疗的疗效。后续用 siRNA 敲低 Ccl20 也证明抗肿瘤功效有所改善。我们的结果揭示了 CCR6 作为 Treg 诱导的免疫抑制的标记物和调节剂，并确定了针对 Treg 免疫抑制活性的代谢决定因素的方法。

Regulatory T cells (Tregs) are important players in the tumor microenvironment. However, the mechanisms behind their immunosuppressive effects are poorly understood. We found that CCR6-CCL20 activity in tumor-infiltrating Tregs is associated with greater glycolytic activity and ablation of Ccr6 reduced glycolysis and lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive activity towards CD8+ T cells was abrogated in Ccr6-/- Tregs due to reduction in activation-induced glycolysis. Furthermore, Ccr6-/- mice exhibited improved survival across multiple tumor models compared to wildtype mice, and Treg and CD8+ T-cell depletion abrogated the improvement. In addition, Ccr6 ablation further promoted the efficacy of anti-PD-1 therapy in a preclinical glioma model. Follow-up knockdown of Ccl20 with siRNA also demonstrated improvement in antitumor efficacy. Our results unveil CCR6 as a marker and regulator of Treg-induced immunosuppression and identify approaches to target the metabolic determinants of Treg immunosuppressive activity.